Diabetes Core Update March 2025 — Episode Summary

Podcast: Diabetes Core Update
Date: March 4, 2025
Hosts: Dr. Neil Skolnik & Dr. John J. Russell
Special Guests: Dr. Christopher Kramer, Dr. Christine Roumie
Duration: ~34 minutes

Episode Overview

This episode of Diabetes Core Update reviews and discusses five key, clinically relevant articles recently published in the American Diabetes Association’s journals and other major medical journals. The topics include diabetes remission, new therapeutics for heart failure with preserved ejection fraction (HFpEF), SGLT2 inhibitor comparisons for kidney outcomes, the renal benefits of tirzepatide, and the risks of peripheral arterial disease events with SGLT2 inhibitors versus DPP4 inhibitors in diabetes patients.

The episode is particularly valuable for clinicians wishing to enhance their understanding of evolving diabetes management strategies, with incisive interpretation, practical takeaways, and expert interviews.

Key Discussion Points and Insights

1. Dapagliflozin + Caloric Restriction for Remission of Early Type 2 Diabetes

Source: BMJ
Segment: [00:02–07:04]

• Study Overview: Randomized, placebo-controlled trial (n=328, China) compared dapagliflozin (10mg/day) plus moderate caloric restriction (500–750 calories below baseline intake) to caloric restriction + placebo in adults with <6 years’ diabetes (avg. 0.3 years diagnosis, BMI >25).
• Definition of Remission: A1C <6.5%, fasting plasma glucose <126 mg/dL, without antidiabetic drugs for ≥2 months.
• Primary Result: 44% remission in dapagliflozin group vs. 28% in placebo (RR 1.5; P=0.002, 56% higher likelihood of remission).
• Secondary Outcomes: Greater weight loss, improved insulin resistance (HOMA-IR), body fat, systolic BP, and other metabolic risk factors for dapagliflozin.
• Notable Quote:

  "This is the holy grail, right? Can we find something, as soon as we diagnose someone with diabetes, that can change the course? ... If a small dose of this oral agent would decrease diabetes by 44%, I'd be like, wow, this is amazing."
  — Dr. John Russell [03:40]

• Caveats:
  • Study population: Almost all new-onset, mostly men, average BMI <30, homogenous Chinese cohort.
  • May not generalize to older, heavier, or more diverse populations or those with longer-standing diabetes.
  • "It's exciting, but this isn't the patient who's had diabetes for five years with a BMI of 34." — Dr. Russell [06:32]
• Clinical Implication: In select, early-diagnosis patients (lower BMI, short diabetes duration), dapagliflozin + diet may offer a realistic chance of remission.

2. Tirzepatide for HFpEF and Obesity

Source: The New England Journal of Medicine
Guest Expert: Dr. Christopher Kramer
Segment: [07:04–14:09]

• Background: Few therapies for HFpEF (Heart Failure with Preserved Ejection Fraction); prior work showed symptom benefits with semaglutide.
• SUMMIT Trial: 731 patients, HFpEF (EF ≥50%), BMI ≥30, randomized to tirzepatide vs. placebo for ≥52 weeks.
• Primary Endpoint: Composite CV death & heart failure events (hospitalizations, increased diuretic needs).
• Findings:
  • Hazard ratio 0.64 for primary endpoint (driven by fewer heart failure events, notably fewer hospitalizations; no difference in CV death).
  • Symptom improvement: Significantly greater increases in Kansas City Cardiomyopathy Questionnaire (KCCQ) scores in tirzepatide vs. placebo.
  • Effective over 52–104 weeks.
• Notable Quotes:

  "Patients definitely felt better on drug." — Dr. Kramer [11:04]
  "GLP1s have multiple beneficial effects...improving symptoms, reducing heart failure hospitalization...another arrow in the armamentarium." — Dr. Kramer [12:14]

• Clinical Implication: Tirzepatide adds another evidence-based option for HFpEF in obese patients; joins SGLT2s and ARNI’s as new standards.
• Host Perspective:

  "We've gone from zero to 60 very quickly over the last three or four years in HFpEF." — Dr. Skolnik [13:34]

3. Empagliflozin vs. Dapagliflozin: Kidney Outcomes

Source: JAMA Internal Medicine
Segment: [14:11–16:42]

• Study Design: Target trial emulation using Danish registry data (2014-2020, 32,000+ EMPA, 17,000+ DAPA initiators; mean eGFR 88, mean age 63).
• Outcome: 6-year risks of acute kidney injury, chronic kidney disease, albuminuria/progression were comparable between EMPA and DAPA.
• Discussion:
  • Both are strong SGLT2 options for kidney protection.
  • "This is really overwhelming data...you can use either medicine very confidently and get the same effect." — Dr. Russell [15:31]
  • Not all SGLT2 inhibitors may have the same effect—class effect should not be assumed for all without supporting data.
  • "Anytime that we can protect someone's kidneys, it's very exciting." — Dr. Russell [16:09]
• Clinical Takeaway: Both empagliflozin and dapagliflozin are equally valid for kidney protection; choice can be tailored to patient, formulary, or cost needs.

4. Tirzepatide and Reduced Albuminuria in Type 2 Diabetes

Source: Diabetes Care
Segment: [16:43–18:50]

• Study: Pooled post hoc analysis from SURPASS 1–5 trials; evaluated tirzepatide (5/10/15 mg) on urine albumin-creatinine ratio (UACR).
• Results:
  • Dose-dependent decreases in UACR:
    • 5mg: Δ= -19.3%
    • 10mg: -22%
    • 15mg: -26.3%
  • Effects more pronounced in those with baseline UACR ≥30 mg/g.
  • Weight loss contributed to about half the reduction in albuminuria.
  • No difference in eGFR vs. comparators at weeks 40–42.
• Host Comment:

  "Tirzepatide has beneficial effects on the kidney, decreases albuminuria...moving forward, is this going to be the four pillars of kidney care, like heart failure?" — Dr. Skolnik [19:32]

• Clinical Implication: Confirms GLP1 receptor agonists’ emerging renal benefit, though effects on eGFR decline/progression still need to be studied directly; may soon become standard elements in diabetic kidney disease care.

5. SGLT2 Inhibitors vs DPP4 Inhibitors and Risk of Peripheral Artery Disease (PAD) Surgical Events

Source: Diabetes Care
Guest Expert: Dr. Christine Roumie
Segment: [22:49–34:16]

• Why the Study: SGLT2 inhibitors’ initial trials (like CANVAS) raised signals about higher amputation risks, leading to regulatory warnings. Uncertainty remains on class-wide risk.
• Study Design: Real-world VA data (n=75,000+ per group, mean age 69, mostly men/older/long-duration diabetes), SGLT2i vs DPP4i as add-on meds, looked at amputations + vascular procedures.
• Findings:
  • SGLT2i associated with a ~15–16% higher hazard for PAD-related surgical events (HR ~1.15 vs DPP4i).
  • Absolute risk difference: ~1 additional event per 1,000 person-years (11 vs 10/1,000 person-years).
  • Mostly empagliflozin used; not driven by canagliflozin alone.
• Notable Quotes:

  "We need to be really thoughtful and risk stratify...not just kind of blanket them all with SGLT2, particularly older people who might have had diabetes in excess of 10 years." — Dr. Roumie [32:13] "As clinicians, we're always weighing benefit and risk. The more we know about the risk side, the better we're able to proceed." — Dr. Skolnik [33:39]

• Practice Pearl: Use SGLT2s judiciously, especially in older, high-risk-for-PAD patients; consider screening (ABI) before starting SGLT2 if risk is suspected.
• Mechanisms for Increased PAD Risk: Uncertain—possible hemodynamic or volume-related changes; more research needed.

Memorable Quotes

• On Diabetes Remission:

  "If you could really supercharge someone and say if you really get religion about diet and calories and try this medicine, it might work."
  — Dr. Russell [05:58]

• On Broadening Treatment Options in HFpEF:

  "We've gone from zero to 60 very quickly...we've had four pillars of therapy in HFpEF for the last couple of years."
  — Dr. Kramer [13:34]

• On New Kidney Therapies:

  "It's exciting to be part of this march of scientific progress...part of the approach for at least some people with chronic kidney disease and diabetes is going to be the GLP1s and the GLP1 dual agonists."
  — Dr. Skolnik [19:32]

• On SGLT2 Inhibitor PAD Risk:

  "If there are a thousand people using SGLT2 for a year...there may be one additional peripheral vascular event."
  — Dr. Roumie [31:34]

Timestamps for Important Segments

• Dapagliflozin + Caloric Restriction for Remission: [00:02–07:04]
• Tirzepatide for HFpEF (Guest: Dr. Christopher Kramer): [07:04–14:09]
• Empagliflozin vs. Dapagliflozin for Kidney Outcomes: [14:11–16:42]
• Tirzepatide Reduces Albuminuria: [16:43–18:50]
• SGLT2 vs DPP4 Risk of PAD (Guest: Dr. Christine Roumie): [22:49–34:16]

Clinical Takeaways

• Early, aggressive intervention (diet + SGLT2i) may remission select new-onset T2Ds.
• Tirzepatide adds a valuable option for HFpEF—improves both symptoms and events.
• Empagliflozin and Dapagliflozin are equivalent for kidney protection; class effect may not generalize to all SGLT2s.
• GLP1 (tirzepatide) therapies reduce albuminuria; CKD progression impact under current study.
• SGLT2i can increase PAD risk; risk stratification and individualization are crucial in high-risk populations.

For full article access, visit: diabetesjournals.org

Hosts encourage:

"Keep listening and keep learning." — Dr. Russell [34:34]